1. Field of the Invention
The present invention provides novel Interheteroaryl 7-Oxabicyclo [2.2.1] heptane oxazoles useful as Prostaglandin F2xcex1 (FP receptor) antagonists. The present invention also provides a method of synthesizing such novel compounds.
2. Description of Related Art
Prostaglandin F2xcex1 antagonists are reported in U.S. Pat. Nos. 4,632,928; 5,747,660; and 5,955,575. The PGF2xcex1 antagonists of U.S. Pat. No. 4,632,928 are pyrazole derivatives having an ergoline skeleton. The PGF2xcex1 antagonist of U.S. Pat. No. 5,747,660 is a prostaglandin F2xcex1 receptor regulatory protein (FPRP) which is able to inhibit the binding of PGF2xcex1 to its receptor. The inventors of this patent state that the prostaglandin F2xcex1 antagonist of their invention is believed to be the first selective prostaglandin F2xcex1 antagonist discovered. U.S. Pat. No. 5,955,575 describes peptide sequences derived from the prostaglandin receptor F2xcex1 and the G-protein, Gxcex1q, as selective inhibitors of signal transduction involved in the stimulation of the prostaglandin receptor F2xcex1.
Interphenylene 7-Oxabicyclo [2.2.1] heptane oxazoles, useful as Thromboxane A2 receptor antagonists are reported in U.S. Pat. Nos. 5,100,889 and 5,153,327, European Patent Application 0 391 652 and J. Med. Chem. 1993, 36, 1401-1417.
Thromboxane A2 receptor antagonists, e.g. 7-oxabicycloheptyl substituted heterocyclic amide prostaglandin analogs, alone, or in combination with anti-inflammatory agents are useful in treating ulcerative gastrointestinal conditions and dysmenorrhea as disclosed in European Patent Application 0 448 274 and U.S. Pat. No. 5,605,917.
The invention relates to novel Interheteroaryl 7-Oxabicyclo [2.2.1] heptane oxazoles useful as PGF2xcex1 antagonists, the synthesis thereof, and their use in treating diseases and conditions, where PGF2xcex1 is involved.
The novel compounds of the present invention are represented by the general formula I. 
wherein m is an integer of from 1 to 3, preferably 1 or 2;
n is 0 or an integer of from 1 to 4, preferably from 2 to 4;
R is selected from the group consisting of CO2H, CO2R6, CH2OH, CH2OR6 
xe2x80x83and CONR3R4;
R1 and R2 are independently selected from the group consisting of H, R6, C1-C6 alkenyl, C1-C6 alkynyl, C3-C7 cycloalkyl, C4-C12 alkylcycloalkyl, C6-C10 aryl, C7-C12 alkylaryl radicals and heteroatom-substituted derivatives thereof, wherein one or more of the hydrogen or carbon atoms in said radicals is replaced with a halogen, nitrogen or sulfur-containing radical, e.g. F, Cl, Br, I, NO2, N(R7)2, CON(R7)2, SR7 and CN, wherein R7 is selected from the group consisting of H and C1-C6 alkyl; R3 and R4 are independently selected from the group consisting of H and R6; and X is selected from the group consisting of H, R6, hydroxy, halogen, COOR6, NO2, N(R6)2, CON(R6)2, SR6, CN and OR6 wherein R6 is C1-C6 alkyl; Y is O or S; Z is N or CH and pharmaceutically acceptable salts thereof.
These compounds are especially useful for treating a number of PGF2xcex1xe2x80x94mediated disease responses. For instance, prostaglandins play an important role in inflammatory reactions relating to rheumatoid arthritis and psoriasis, reproductive disorders, bronchoconstrictive disorders (asthma), excessive bone breakdown (osteoporosis), peptic ulcers, heart disease, platelet aggregation and thrombosis.